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Misinterpretation of the determinants of elevated forward wave amplitude inflates the role of the proximal aorta

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Abstract
Background: The hemodynamic basis for increased pulse pressure (PP) with aging remains controversial. The classic paradigm attributes a predominant role to increased pulse wave velocity (PWV) and premature wave reflections (WRs). A controversial new paradigm proposes increased forward pressure wave amplitude (FWA), attributed to proximal aortic characteristic impedance (Z(c)), as the predominant factor, with minor contributions from WRs. Based on theoretical considerations, we hypothesized that (rectified) WRs drive the increase in FWA, and that the forward pressure wave does not depend solely on the interaction between flow and Z(c) (QZc product). Methods and Results: We performed 3 substudies: (1) open-chest anesthetized dog experiments (n=5); (2) asymmetric T-tube model-based study; and (3) human study in a diverse clinical population (n=193). Animal experiments demonstrated that FWA corresponds to peak QZc only when WRs are minimal. As WRs increased, FWA was systematically greater than QZc and peaked well after peak flow, analogous to late-systolic peaking of pressure attributable to WRs. T-tube modeling confirmed that increased/ premature WRs resulted in increased FWA. Magnitude and timing of WRs explained 80.8% and 74.3% of the variability in the difference between FWA and peak QZc in dog and human substudies, respectively. Conclusions: Only in cases of minimal reflections does FWA primarily reveal the interaction between peak aortic flow and proximal aortic diameter/stiffness. FWA is strongly dependent on rectified reflections. If interpreted out of context with the hemodynamic principles of its derivation, the FWA paradigm inappropriately amplifies the role of the proximal aorta in elevation of FWA and PP.
Keywords
arterial stiffness, characteristic impedance, REFLECTION, FRAMINGHAM, STIFFNESS, PULSATILE ARTERIAL LOAD, AGE-RELATED-CHANGES, NONINVASIVE EVALUATION, SYSTOLIC HYPERTENSION, INPUT IMPEDANCE, BLOOD-PRESSURE, forward wave amplitude, ventricular-arterial coupling, wave reflections, T-TUBE MODEL

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Chicago
Phan, Timothy S, John KJ Li, Patrick Segers, and Julio Chirinos Medina. 2016. “Misinterpretation of the Determinants of Elevated Forward Wave Amplitude Inflates the Role of the Proximal Aorta.” Journal of the American Heart Association 5 (2).
APA
Phan, T. S., Li, J. K., Segers, P., & Chirinos Medina, J. (2016). Misinterpretation of the determinants of elevated forward wave amplitude inflates the role of the proximal aorta. JOURNAL OF THE AMERICAN HEART ASSOCIATION, 5(2).
Vancouver
1.
Phan TS, Li JK, Segers P, Chirinos Medina J. Misinterpretation of the determinants of elevated forward wave amplitude inflates the role of the proximal aorta. JOURNAL OF THE AMERICAN HEART ASSOCIATION. 2016;5(2).
MLA
Phan, Timothy S et al. “Misinterpretation of the Determinants of Elevated Forward Wave Amplitude Inflates the Role of the Proximal Aorta.” JOURNAL OF THE AMERICAN HEART ASSOCIATION 5.2 (2016): n. pag. Print.
@article{8057826,
  abstract     = {Background: The hemodynamic basis for increased pulse pressure (PP) with aging remains controversial. The classic paradigm attributes a predominant role to increased pulse wave velocity (PWV) and premature wave reflections (WRs). A controversial new paradigm proposes increased forward pressure wave amplitude (FWA), attributed to proximal aortic characteristic impedance (Z(c)), as the predominant factor, with minor contributions from WRs. Based on theoretical considerations, we hypothesized that (rectified) WRs drive the increase in FWA, and that the forward pressure wave does not depend solely on the interaction between flow and Z(c) (QZc product). 
Methods and Results: We performed 3 substudies: (1) open-chest anesthetized dog experiments (n=5); (2) asymmetric T-tube model-based study; and (3) human study in a diverse clinical population (n=193). Animal experiments demonstrated that FWA corresponds to peak QZc only when WRs are minimal. As WRs increased, FWA was systematically greater than QZc and peaked well after peak flow, analogous to late-systolic peaking of pressure attributable to WRs. T-tube modeling confirmed that increased/ premature WRs resulted in increased FWA. Magnitude and timing of WRs explained 80.8% and 74.3% of the variability in the difference between FWA and peak QZc in dog and human substudies, respectively. 
Conclusions: Only in cases of minimal reflections does FWA primarily reveal the interaction between peak aortic flow and proximal aortic diameter/stiffness. FWA is strongly dependent on rectified reflections. If interpreted out of context with the hemodynamic principles of its derivation, the FWA paradigm inappropriately amplifies the role of the proximal aorta in elevation of FWA and PP.},
  articleno    = {e003069},
  author       = {Phan, Timothy S and Li, John KJ and Segers, Patrick and Chirinos Medina, Julio},
  issn         = {2047-9980},
  journal      = {JOURNAL OF THE AMERICAN HEART ASSOCIATION},
  keywords     = {arterial stiffness,characteristic impedance,REFLECTION,FRAMINGHAM,STIFFNESS,PULSATILE ARTERIAL LOAD,AGE-RELATED-CHANGES,NONINVASIVE EVALUATION,SYSTOLIC HYPERTENSION,INPUT IMPEDANCE,BLOOD-PRESSURE,forward wave amplitude,ventricular-arterial coupling,wave reflections,T-TUBE MODEL},
  language     = {eng},
  number       = {2},
  pages        = {12},
  title        = {Misinterpretation of the determinants of elevated forward wave amplitude inflates the role of the proximal aorta},
  url          = {http://dx.doi.org/10.1161/JAHA.115.003069},
  volume       = {5},
  year         = {2016},
}

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